The dissociation and denaturation properties of the principal coat protein clathrin have been studied in urea solution. Low concentration of urea (Less than 3 M) dissociate the light chain, but no denaturation is observed. At higher urea concentrations, two distinct structural changes occur, one between 3 and 6 M and another above 7 M urea. Basic compounds, e.g. biologic amines are found to stabilize the coat structure of clathrin in baskets as well as in coated vesicles. The degree of stabilization increases with the increase in the number of amino groups and does not depend upon the number of intervening methylene groups. The contribution of the hydrophobic interaction toward the stability of the coat structure has been identified by the effect of lyotropic salts on the properties of the baskets and coated vesicles. The lyotropic salts affect the organized structure of the lipid vesicles (liposomes) similarly to that on proteins. This study of [35S]methionine incorporation into bovine thyroid slices suggests that coated vesicles do not have a major role in exocytosis of newly synthesized thyroglobulins from thyroid epithelial cells. [35S] incorporation into rat liver yields data which are compatible with the concept that the coat protein, clathrin, may be preferentially recycled during coated vesicle turnover as an indication of what may occur during receptor-mediated endocytosis.